Lin Shu-Fu, Hsueh Chuen, Chen Wei-Yi, Chou Ting-Chao, Wong Richard J
Division of Endocrinology and Metabolism, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City 23652, Taiwan.
College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
Cancers (Basel). 2025 Jan 22;17(3):359. doi: 10.3390/cancers17030359.
Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies and has a poor prognosis. Ataxia telangiectasia mutated and Rad3 related (ATR) is a key regulator for the DNA damage response and a potential target to treat cancer.
We assessed the efficacy of BAY 1895344, an ATR inhibitor, in three ATC cell lines.
BAY 1895344 caused dose-response cytotoxicity in three ATC cell lines. BAY 1895344 induced S-phase and G2-phase arrest, activated caspase-3 activity and induced apoptosis in ATC cells. BAY 1895344 meaningfully retarded the tumor growth of an ATC xenograft model. BAY 1895344 therapy, combined with dabrafenib and trametinib, had synergism in vitro and revealed robust tumor growth suppression in vivo in two xenograft models of ATC harboring mutant . Furthermore, the combination of BAY 1895344 with lenvatinib was more effective than either agent alone in a xenograft model of ATC.
These results reveal that BAY 1895344 has potential in treating ATC.
间变性甲状腺癌（ATC）是最具侵袭性的人类恶性肿瘤之一，预后较差。共济失调毛细血管扩张症突变和Rad3相关蛋白（ATR）是DNA损伤反应的关键调节因子，也是治疗癌症的潜在靶点。
我们评估了ATR抑制剂BAY 1895344在三种ATC细胞系中的疗效。
BAY 1895344在三种ATC细胞系中引起剂量反应性细胞毒性。BAY 1895344诱导ATC细胞S期和G2期阻滞，激活caspase-3活性并诱导细胞凋亡。BAY 1895344显著抑制了ATC异种移植模型的肿瘤生长。BAY 1895344与达拉非尼和曲美替尼联合治疗在体外具有协同作用，并在两种携带突变体的ATC异种移植模型中显示出强大的体内肿瘤生长抑制作用。此外，在ATC异种移植模型中，BAY 1895344与乐伐替尼联合使用比单独使用任何一种药物都更有效。
这些结果表明BAY 1895344在治疗ATC方面具有潜力。
